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Bone Abstracts (2017) 6 P034 | DOI: 10.1530/boneabs.6.P034

1Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 2Rare Diseases and Medical Genetic Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Division of Immunology and Infectious Diseases Department of Pediatrics, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4Department of Pediatric Hemathology and Oncology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 5Histopathology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.

Objectives: Gorham-Stout disease (GSD) is a very rare disorder characterized by extensive angiomatous proliferation and progressive osteolysis without new bone formation. Only ~200 patients were reported. The quality of life is very poor since patients display pain, fractures, functional impairment and swelling of the affected regions. The ethiology of GSD is unknown. We aim to investigate the bone phenotype and to identify molecular and cellular defects in GSD patients.

Methods: Eight patients were recruited for this study. Bone biopsy analysis was performed. Bone turnover’s markers were analysed by ELISA assay. In vitro osteoclast and osteoblast cultures were performed to evaluate alterations of differentiation, morphology and activity. Osteoclast and osteoblast’s gene expression was evaluated by Real-Time RT-PCR.

Results: Bone biopsy analysis revealed fibrous tissue with dilated blood vessel as well as evidence of very active osteoclast resorption. A 10-fold increase of osteoclast number with high levels of serum ICTP was observed in patients. Osteoclast precursors (pOCs) isolated from patients showed a approximately twofold increased ability to differentiate into osteoclasts (412.6±69.58 vs 887.7±56.35; P<0.03), with higher number of nuclei per cell. About 75% of affected osteoclasts displayed a more motile phenotype. Real-Time RT-PCR expression analysis revealed that patients’ osteoclasts displayed a transcriptional increase of TCIRG1, CTSK and MMP9 genes. pOCs from healthy donors treated with serum from patients showed an increase of osteoclastogenesis compared to pOCs treated with controls’ serum. Bone Marrow MSC isolated from a patient displayed the characteristic spindle-shaped morphology and the same immunophenotype as healthy donors (HD)-MSCs. After incubation with osteogenic medium, GSD-MSCs demonstrated reduced ALP activity and expression compared with HD-MSCs.

Conclusions: These results suggest that in Gorham-Stout disease the alteration of bone remodelling activity is related to bone cell autonomous defects and systemic factors. Understanding the molecular and cellular defects in GSD patients will allow to have a correct diagnosis and new therapeutic options for this rare disease.

Disclosure: The authors declared no competing interests.

Volume 6

8th International Conference on Children's Bone Health


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